A new repository antimalarial agent, CI-564, used in a field trial in New Guinea

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Abstract
A comparative study of 3 repository antimalarial agents was conducted in a malarious area of New Guinea. Each of 3 comparable groups of about 200 people was given one of the following CI-501 (cycloguanil pamoate), CI-556 [DADDS N,N[image]-diacetyl-4,4[image]-diaminodiphenylsulfone] or a combination of these, CI-564. The drugs or drug combinations were administered as single deep intragluteal injections; in the CI-501 group a single oral dose of amodiaquine was administered concurrently. There was no evidence of any systemic toxicity and localized reactions were mild. The combination CI-564 provided a longer period of protection against Plasmodium falciparum than either of its component drugs, cycloguanil pamoate and DADDS, used alone. The first patent P. falciparum infections in the CI-564 group were seen 90 days after treatment, the prevalence being about 15% of the pre-therapy level; the prevalence of infections in the other 2 groups was 60-70% of the pre-therapy level. The combination CI-564 and the cycloguanil component used alone provided a similar degree of protection against P. vivax, the period of complete protection against patent infections being 60 to 90 days. DADDS had an indefinite and short-lived effect against P. vivax infections, pre-therapy levels being attained 30 days after treatment. Drug susceptibility tests were conducted before injection and 60 to 180 days after it. No evidence of strain resistance to proguanil was found before treatment was begun. A small proportion of tested subjects showed diminished susceptibility to proguanil after the injection, but this proportion did not increase towards the end of the study. At the dosages administered, the combination CI-564 had a greater antimalarial effect against P. falciparum than either of its component drugs used alone.

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